Maternal anxiety and infants' hippocampal development: timing matters

Abstract

Exposure to maternal anxiety predicts offspring brain development. However, because children's brains are commonly assessed years after birth, the timing of such maternal influences in humans is unclear. This study aimed to examine the consequences of antenatal and postnatal exposure to maternal anxiety upon early infant development of the hippocampus, a key structure for stress regulation. A total of 175 neonates underwent magnetic resonance imaging (MRI) at birth and among them 35 had repeated scans at 6 months of age. Maternal anxiety was assessed using the State-Trait Anxiety Inventory (STAI) at week 26 of pregnancy and 3 months after delivery. Regression analyses showed that antenatal maternal anxiety did not influence bilateral hippocampal volume at birth. However, children of mothers reporting increased anxiety during pregnancy showed slower growth of both the left and right hippocampus over the first 6 months of life. This effect of antenatal maternal anxiety upon right hippocampal growth became statistically stronger when controlling for postnatal maternal anxiety. Furthermore, a strong positive association between postnatal maternal anxiety and right hippocampal growth was detected, whereas a strong negative association between postnatal maternal anxiety and the left hippocampal volume at 6 months of life was found. Hence, the postnatal growth of bilateral hippocampi shows distinct responses to postnatal maternal anxiety. The size of the left hippocampus during early development is likely to reflect the influence of the exposure to perinatal maternal anxiety, whereas right hippocampal growth is constrained by antenatal maternal anxiety, but enhanced in response to increased postnatal maternal anxiety.

The Placenta as a Mediator of Stress Effects on Neurodevelopmental Reprogramming

“…The result is for a potential fetal glucocorticoid overexposure to impact ongoing developmental events including a restriction of fetal growth, premature maturation of proliferative neural precursors, and altered HPA axis development (Seckl and Holmes, 2007). Notably, these predicted effects are consistent with the reduced perinatal brain volumetric findings in association with maternal stress described earlier (Li et al, 2012;Lou et al, 1994;Qiu et al, 2013). In addition to the potential for actions of excess glucocorticoids on the developing fetal brain, excess glucocorticoids also act within the placenta to have an impact on endocrine functions, thus compromising placental growth, vascularization, and nutrient transport (Hewitt et al, 2006;Wyrwoll et al, 2009).…”

“…These studies reported delayed overall brain growth, limbic systemspecific volumetric changes, and white matter abnormalities (Li et al, 2012;Lou et al, 1994;Qiu et al, 2013Qiu et al, , 2015Rifkin-Graboi et al, 2013). Such early observations appear to persist into childhood and adolescence, are correlated with affective problems, and may contribute to symptoms in patients with schizophrenia and autism (Buss et al, 2010(Buss et al, , 2012Davis et al, 2013;Du et al, 2013;Sarkar et al, 2014;Zikopoulos and Barbas, 2010).…”

Mother nurture and the social definition of neurodevelopment

“…Because maternal mood generally remains stable across the peripartum period, the Lupien et al (3) findings might reflect a prenatal maternal mood, thus resolving the apparent contradiction. In support of this idea, postnatal maternal mood, controlling for prenatal mood, predicts hippocampal growth trajectories (11). Similarly, prenatal maternal cortisol levels associate with the amygdala but not hippocampus volume in middle childhood (10).…”

Intergenerational Transmission of Stress in Humans

“…A separate study similarly observed an effect of prenatal maternal anxiety on neonatal frontal cortical thickness that was moderated by functional variants of the catechol-O-methyltransferase (COMT) gene, which regulates catecholamine signaling and is implicated in anxiety, pain, and stress responsivity (Qiu et al, 2014). Furthermore, a strong positive association was observed between postnatal maternal anxiety and offspring right hippocampal growth and a strong negative association between postnatal maternal anxiety and offspring left hippocampal volume at 6 months of age (Pruessner et al, 2008;Qiu et al, 2013). Notably, the frontal cortex and hippocampus have been implicated in fear and stress reactivity, trait anxiety, and psychopathology, including PTSD (Rusch et al, 2001;Shin et al, 2006;Pruessner et al, 2008).…”